Smooth muscle cell immediate-early gene and growth factor activation follows vascular injury: A putative in vivo mechanism for autocrine growth

Joseph M. Miano, Niksa Vlasic, Robert R. Tota, Michael B. Stemerman

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

To understand the molecular events governing smooth muscle cell (SMC) proliferation in vivo, immediate-early gene (IEG) expression was assessed and related to growth factor ligand and receptor mRNA and SMC DNA synthesis after aortic injury. Balloon catheter injury evoked increases in SMC c-myc and thrombospondin (tsp) within 2 hours. The induction of these IEGs was followed by elevated transcripts to platelet-derived growth factor-A (PDGF-A), transforming growth factor-01 (TGF-β1) and a basic fibroblast growth factor (bFGF) receptor. Whereas PDGF type-β receptor mRNA was demonstrated in SMCs from control and balloon-injured aortas, no detectable signal was observed for the PDGF type-α receptor. To explore the potential linkage between IEG products and growth factor mRNA expression, cycloheximide was employed to block early protein synthesis after balloon injury. Induction of PDGF-A and TGF-β1 was attenuated by cycloheximide, but bFGF induction was unaffected. Moreover, cycloheximide superinduced IEGs and revealed PDGF-B transcripts, which were otherwise undetected. Seven days after aortic injury, a spontaneous increase in c-myc and tsp mRNA was noted. This IEG reactivation was followed 12 hours later by a twofold increase in SMC DNA synthesis. These findings corroborate an autocrine mode of SMC proliferation in vivo and suggest that IEG products may control such growth by stimulating growth factor genes.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume13
Issue number2
DOIs
StatePublished - 1993

Keywords

  • Autocrine growth
  • Growth factors
  • Immediate-early gene
  • Smooth muscle cell proliferation
  • Vascular injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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